FEVER

Med. Bernardo Dmaso Mata

Body temperature reflects the difference between heat production
and heat loss and varies with exercise and extremes of environmental
temperature.
Properly protected, the body can function in environmental conditions
that range from 50C (58F) to +50C (+122F).
Individual body cells, however, cannot tolerate such a wide range of
temperatures: at 1C (+30F) ice crystals form, and at +45C (+113F),
cell proteins coagulate.
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THERMOREGULATION
Core body temperature is a reflection of the balance between heat
gain and heat loss by the body. Metabolic processes produce heat,
which must be dissipated.
The hypothalamus is the thermal control center for the body,
receives information from peripheral and central thermoreceptors,
and compares that information with its temperature set point.
Heat loss occurs through transfer of body core heat to the surface
through the circulation. Heat is lost from the skin through radiation,
conduction, convection, and evaporation.
An increase in core temperature is effected by vasoconstriction and
shivering, a decrease in temperature by vasodilation and sweating.
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Fever represents an increase in body temperature that results from
a cytokine-induced increase in the set-point of the thermostatic
center in the hypothalamus.
Fever is a nonspecific response that is mediated by endogenous
pyrogens released from host cells in response to infectious or
noninfectious disorders.
The development of fever involves a prodrome, a chill during which
the temperature rises until it reaches the new hypothalamic set-
point, a flush during which the skin vessels dilate and the
temperature begins to fall, and a period of defervescence that is
marked by sweating.
Fever is resolved when the condition causing the increase in the
set-point of the thermostatic center in the hypothalamus is
resolved.
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Core body temperature is normally maintained within a range of
36.0C to 37.5C (97.0F to 99.5F).
Core body and skin temperature are sensed and integrated by
thermoregulatory regions in the hypothalamus and other brain
structures that function to modify heat production and heat loss as
a means of regulating body temperature.
Most of the bodys heat is produced by metabolic processes that
occur within deeper core structures (i.e., muscles and viscera) of
the body.
The sympathetic neurotransmitters (epinephrine and
norepinephrine) and thyroid hormone act at the cellular level to
shift body metabolism to heat production, whereas shivering and
chattering of the teeth use the heat liberated from involuntary
muscle movements to increase body temperature.
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Most of the bodys heat losses occur at the skin surface as heat
from the blood moves through the skin and from there into the
surrounding environment. Heat is lost from the skin through
radiation, conduction, convection, and evaporation of perspiration
and sweat.
Contraction of the pilomotor muscles of the skin aids in heat
conservation by reducing the surface area available for heat loss.
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Mechanisms
Fever, or pyrexia, describes an elevation in body temperature that is
caused by an upward displacement of the thermostatic set-point of
the hypothalamic thermoregulatory center.
Many proteins, breakdown products of proteins, and certain other
substances released from bacterial cell membranes can cause a
change in the set-point to rise.
Fever is resolved or broken when the condition that caused the
increase in the set-point is removed.
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Mechanisms
Fevers that are regulated by the hypothalamus usually do not rise
above 41C (105.8F), suggesting a built-in thermostatic safety
mechanism.
Temperatures above that level are usually the result of
superimposed activity, such as convulsions, hyperthermic states, or
direct impairment of the temperature control center.
FEVER
Mechanisms
Pyrogens are exogenous or endogenous substances that produce
fever.
Exogenous pyrogens are derived from outside the body and include
such substances as bacterial products, bacterial toxins, or whole
microorganisms.
Exogenous pyrogens induce host cells to produce fever-producing
mediators called endogenous pyrogens.
When bacteria or breakdown products of bacteria are present in
blood or tissues, they are engulfed by phagocytic cells of the
immune system.
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Mechanisms
These phagocytic cells digest the bacterial products and then
release pyrogenic cytokines, principally interleukin-1 (IL-1),
interleukin-6 (IL-6), and tumor necrosis factor- (TNF-), into the
bloodstream for transport to the hypothalamus, where they exert
their action.
Prostaglandin E2 (PGE2), which is a metabolite of arachidonic acid
(an intramembrane fatty acid), is considered to be the final fever
mediator in the hypothalamus, induced by these cytokines.
FEVER
Mechanisms
PGE2 binds to receptors in the hypothalamus to induce changes in
its set-point through the second messenger cyclic adenosine
monophosphate (cAMP).
In response to the increase in its thermostatic set-point, the
hypothalamus initiates shivering and vasoconstriction that raise the
bodys core temperature to the new set-point, and fever is
established.
FEVER
Mechanisms
Although the central role of PGE2 in raising the set-point of the
hypothalamic thermoregulatory center and producing fever is not
questioned, recent research suggests that the febrile response to
invading gram-negative bacteria and their products (mainly
endotoxic lipopolysaccharides) is mediated by peripherally rather
than centrally produced PGE2.
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Mechanisms
These pathogens are thought to activate the alternative pathway of
the complement system, which in turn stimulates Kupffer cells (i.e.,
phagocytic cells found on luminal surface of hepatic sinusoids) in
the liver to produce an almost instantaneous release of PGE2.
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Mechanisms
The PGE2 produced by the Kupffer cells is thought to cause an
immediate rise in temperature by activating vagal afferents in the
liver that project to the hypothalamus or by being carried directly to
the hypothalamus by the circulation.
The pyrogenic cytokines (IL-1, IL-2, TNF-) are produced later and
contribute to the continued rise in temperature.
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Mechanisms
In addition to their fever-producing actions, the endogenous
pyrogens mediate a number of other responses.
For example, IL-1 and TNF- are inflammatory mediators that
produce other signs of inflammation such as leukocytosis, anorexia,
and malaise.
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Mechanisms
Many noninfectious disorders, such as myocardial infarction,
pulmonary emboli, and neoplasms, produce fever. In these
conditions, the injured or abnormal cells incite the production of
endogenous pyrogens. For example, trauma and surgery can be
associated with up to 3 days of fever.
Some malignant cells, such as those of leukemia and Hodgkin
disease, secrete chemical mediators that function as endogenous
pyrogens.
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Mechanisms
A fever that has its origin in the central nervous system is
sometimes referred to as a neurogenic fever.
It usually is caused by damage to the hypothalamus due to central
nervous system trauma, intracerebral bleeding, or an increase in
intracranial pressure.
Neurogenic fevers are characterized by a high temperature that is
resistant to antipyretic therapy and is not associated with sweating.
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Fever and hyperthermia refer to an increase in body temperature
outside the normal range.
True fever is a disorder of thermoregulation in which there is an
upward displacement of the set-point for temperature control.
In hyperthermia, the set-point is unchanged, but the challenge to
temperature regulation exceeds the thermoregulatory centers
ability to control body temperature.
FEVER
Fever can be caused by a number of factors, including
microorganisms, trauma, and drugs or chemicals, all of which incite
the release of endogenous pyrogens.
The reactions that occur during fever consist of four stages: a
prodrome, a chill, a flush, and defervescence.
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A fever can follow an intermittent, remittent, sustained, or
recurrent pattern.
The manifestations of fever are largely related to dehydration and
an increased metabolic rate.
Even a low-grade fever in high-risk infants or in the elderly can
indicate serious infection.
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The treatment of fever focuses on modifying the external
environment as a means of increasing heat transfer to the external
environment; supporting the hypermetabolic state that
accompanies fever; protecting vulnerable body tissues; and treating
the infection or condition causing the fever.
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Hyperthermia, which varies in severity based on the degree of core
temperature elevation and the severity of cardiovascular and
nervous system involvement, includes heat cramps, heat
exhaustion, and heatstroke.
Among the factors that contribute to the development of
hyperthermia are prolonged muscular exertion in a hot
environment, disorders that compromise heat dissipation, and
hypersensitivity drug reactions.
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Malignant hyperthermia is an autosomal dominant disorder that
can produce a severe and potentially fatal increase in body
temperature.
The condition commonly is triggered by general anesthetic agents
and muscle relaxants used during surgery.
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The neuroleptic malignant syndrome is associated with neuroleptic
drug therapy and is thought to result from alterations in the
function of the thermoregulatory center or from uncontrolled
muscle contraction.
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